The research proposed is to study the role of costimulatory molecules in the development of cytotoxic T lymphocytes (CTL). CTL are important cells in the immune response to viruses, and hold great promise for immunotherapy of cancer. Costimulatory molecules are known to have a central role in lymphocyte activation, but their role in CTL responses is poorly understood. Animals that have been genetically altered to be deficient in costimulatory molecules will be used to determine the role of these molecules in CTL development. In specific aim I, the CTL response to ovalbumin, expressed by a recombinant vaccinia virus, will be investigated. Ovalbumin was chosen because there are unique reagents available (including transgenic mice) for use in this system. In specific aim II, the role of costimulatory molecules in the immune response to respiratory syncytial virus, an important pathogen in humans, will be determined. These studies will help us to better understand CTL development, and so will help to guide future immunotherapy and vaccine trials.